Medicine and Health Sciences Commons^™

Vulvovaginal Candidiasis: A Review Of The Evidence For The 2021 Centers For Disease Control And Prevention Of Sexually Transmitted Infections Treatment Guidelines., Paul Nyirjesy, Carolyn Brookhart, Gweneth Lazenby, Jane Schwebke, Jack D Sobel

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common cause of vulvovaginal itching and discharge. This article discusses the latest CDC STI Treatment Guidelines for VVC.

METHODS: A literature search of relevant topics was performed, and a team of experts was convened to discuss (1) diagnosis/testing modalities; treatment of (2) uncomplicated VVC , (3) complicated VVC, and (4) VVC caused by non-albicans yeast; (5) alternative treatment regimens; (6) susceptibility testing of yeast; Special Populations: (7) pregnancy and (8) HIV and VVC.

RESULTS: Yeast culture remains the gold standard for diagnoses. Newer molecular assays have been developed for the diagnosis of VVC and …

Comprehensive Analysis Of Opioid Use After Common Elective Outpatient Orthopaedic Surgeries, Michael U Okoli, Alexander J. Rondon, Clay B Townsend, Matthew Sherman, Asif M. Ilyas, Rothman Opioid Foundation

Rothman Institute Papers

Background: Prescription opioid abuse remains an ongoing public health crisis, especially in orthopaedic surgery. The purpose of the present study is to analyze opioid-prescribing patterns and investigate risk factors for prolonged opioid use after common outpatient orthopaedic surgical procedures.

Methods: After institutional review board approval, a review of 1,384 patients undergoing common elective outpatient orthopaedic procedures from January 2018 to June 2019 was conducted. Data on controlled substance prescriptions were obtained from the prescription drug monitoring program website. Statistical analysis was done to identify predictors for a second opioid prescription and prolonged opioid use (>6 months).

Results: Over 10% …

G Protein-Coupled Receptor Kinase 5 Regulates Thrombin Signaling In Platelets Via Par-1., Kate Downes, Xuefei Zhao, Nicholas S Gleadall, Harriet Mckinney, Carly Kempster, Joana Batista, Patrick L Thomas, Matthew Cooper, James V Michael, Roman Kreuzhuber, Katherine Wedderburn, Kathryn Waller, Bianca Varney, Hippolyte Verdier, Neline Kriek, Sofie E Ashford, Kathleen E Stirrups, Joanne L Dunster, Steven E Mckenzie, Willem H Ouwehand, Jonathan M Gibbins, Jing Yang, William J Astle, Peisong Ma

Cardeza Foundation for Hematologic Research

The interindividual variation in the functional response of platelets to activation by agonists is heritable. Genome-wide association studies (GWASs) of quantitative measures of platelet function have identified fewer than 20 distinctly associated variants, some with unknown mechanisms. Here, we report GWASs of pathway-specific functional responses to agonism by adenosine 5'-diphosphate, a glycoprotein VI-specific collagen mimetic, and thrombin receptor-agonist peptides, each specific to 1 of the G protein-coupled receptors PAR-1 and PAR-4, in subsets of 1562 individuals. We identified an association (P = 2.75 × 10-40) between a common intronic variant, rs10886430, in the G protein-coupled receptor kinase 5 gene (GRK5) …

Development Of A Dual Drug-Loaded, Surfactant-Stabilized Contrast Agent Containing Oxygen, Raj Patel, Quezia Lacerda, Brian E Oeffinger, John R. Eisenbrey, Ankit K. Rochani, Gagan Kaushal, Corinne Wessner, Margaret A Wheatley

Department of Radiology Faculty Papers

Co-delivery of cancer therapeutics improves efficacy and encourages synergy, but delivery faces challenges, including multidrug resistance and spatiotemporal distribution of therapeutics. To address these, we added paclitaxel to previously developed acoustically labile, oxygen-core, surfactant-stabilized microbubbles encapsulating lonidamine, with the aim of developing an agent containing both a therapeutic gas and two drugs acting in combination. Upon comparison of unloaded, single-loaded, and dual-loaded microbubbles, size (~1.7 µm) and yield (~2 × 109 microbubbles/mL) (~1.7) were not statistically different, nor were acoustic properties (maximum in vitro enhancements roughly 18 dB, in vitro enhancements roughly 18 dB). Both drugs encapsulated above required doses …

The Efficacy Of Low-Dose Aspirin In Pregnancy Among Women In Malaria-Endemic Countries, Melissa Bauserman, Sequoia I Leuba, Jennifer Hemingway-Foday, Tracy L Nolen, Janet Moore, Elizabeth M Mcclure, Adrien Lokangaka, Antoinette Tsehfu, Jackie Patterson, Edward A Liechty, Fabian Esamai, Waldemar A Carlo, Elwyn Chomba, Robert L Goldenberg, Sarah Saleem, Saleem Jessani, Marion Koso-Thomas, Matthew Hoffman, Richard Derman, Steven R Meshnick, Carl L Bose

Department of Medicine Faculty Papers

Background: Low dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia.

Methods: This is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence …

Troponin Is Unrelated To Outcomes In Heart Failure Patients Discharged From The Emergency Department, Gregory J Fermann, Jon W Schrock, Phillip D Levy, Peter Pang, Javed Butler, Anna Marie Chang, Douglas Char, Deborah Diercks, Jin H Han, Brian Hiestand, Chris Hogan, Cathy A Jenkins, Christy Kampe, Yosef Khan, Vijaya A Kumar, Sangil Lee, Joann Lindenfeld, Dandan Liu, Karen F Miller, W Frank Peacock, Carolyn M Reilly, Chad Robichaux, Russell L Rothman, Wesley H Self, Adam J Singer, Sarah A Sterling, Alan B Storrow, William B Stubblefield, Cheryl Walsh, John Wilburn, Sean P Collins

Department of Emergency Medicine Faculty Papers

Background: Prior data has demonstrated increased mortality in hospitalized patients with acute heart failure (AHF) and troponin elevation. No data has specifically examined the prognostic significance of troponin elevation in patients with AHF discharged after emergency department (ED) management.

Objective: Evaluate the relationship between troponin elevation and outcomes in patients with AHF who are treated and released from the ED.

Methods: This was a secondary analysis of the Get with the Guidelines to Reduce Disparities in AHF Patients Discharged from the ED (GUIDED-HF) trial, a randomized, controlled trial of ED patients with AHF who were discharged. Patients with elevated conventional …

Alpha-Fetoprotein (Afp) And Afp-L3 Is Most Useful In Detection Of Recurrence Of Hepatocellular Carcinoma In Patients After Tumor Ablation And With Low Afp Level, Madison Force, Grace Park, Divya Chalikonda, Christopher G. Roth, Micah Cohen, Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been …

Neuromotor Prosthetic To Treat Stroke-Related Paresis: N-Of-1 Trial, Mijail D. Serruya, Alessandro Napoli, Nicholas Satterthwaite, Joe Kardine, Joseph Mccoy, Namrata Grampurohit, Kiran Talekar, Devon M. Middleton, Feroze Mohamed, Michael Kogan, Ashwini Sharan, Chengyuan Wu, Robert H. Rosenwasser

Department of Neurology Faculty Papers

Background: Functional recovery of arm movement typically plateaus following a stroke, leaving chronic motor deficits. Brain-computer interfaces (BCI) may be a potential treatment for post-stroke deficits

Methods: In this n-of-1 trial (NCT03913286), a person with chronic subcortical stroke with upper-limb motor impairment used a powered elbow-wrist-hand orthosis that opened and closed the affected hand using cortical activity, recorded from a percutaneous BCI comprised of four microelectrode arrays implanted in the ipsilesional precentral gyrus, based on decoding of spiking patterns and high frequency field potentials generated by imagined hand movements. The system was evaluated in a home setting for 12 weeks …

Hur Plays A Role In Double-Strand Break Repair In Pancreatic Cancer Cells And Regulates Functional Brca1-Associated-Ring-Domain-1(Bard1) Isoforms, Aditi Jain, Matthew Mccoy, Carolyn Coats, Samantha Z Brown, Sankar Addya, Carl Pelz, Rosalie C Sears, Charles Yeo, Jonathan R Brody

Department of Surgery Faculty Papers

Human Antigen R (HuR/ELAVL1) is known to regulate stability of mRNAs involved in pancreatic ductal adenocarcinoma (PDAC) cell survival. Although several HuR targets are established, it is likely that many remain currently unknown. Here, we identified BARD1 mRNA as a novel target of HuR. Silencing HuR caused a >70% decrease in homologous recombination repair (HRR) efficiency as measured by the double-strand break repair (pDR-GFP reporter) assay. HuR-bound mRNAs extracted from RNP-immunoprecipitation and probed on a microarray, revealed a subset of HRR genes as putative HuR targets, including the BRCA1-Associated-Ring-Domain-1 (BARD1) (p < 0.005). BARD1 genetic alterations are infrequent in PDAC, and its context-dependent upregulation is poorly understood. Genetic silencing (siRNA and CRISPR knock-out) and pharmacological targeting of HuR inhibited both full length (FL) BARD1 and its functional isoforms (α, δ, Φ). Silencing BARD1 sensitized cells to olaparib and oxaliplatin; caused G2-M cell cycle arrest; and increased DNA-damage while decreasing HRR efficiency in cells. Exogenous overexpression of BARD1 in HuR-deficient cells partially rescued the HRR dysfunction, independent of an HuR pro-oncogenic function. Collectively, our findings demonstrate for the first time that BARD1 is a bona fide HuR target, which serves as an important regulatory point of the transient DNA-repair response in PDAC cells.

Safety And Efficacy Of Colchicine In Covid-19 Patients: A Systematic Review And Meta-Analysis Of Randomized Control Trials, Farah Yasmin, Hala Najeeb, Abdul Moeed, Wardah Hassan, Mahima Khatri, Muhammad Sohaib Asghar, Ahmed Kunwer Naveed, Waqas Ullah, Salim Surani

Department of Medicine Faculty Papers

Background: Colchicine has been used an effective anti-inflammatory drug to treat gout diseases. Owing to its pharmacodynamic of inhibiting interleukins, it has been repurposed to target the cytokine storm post-SARS-CoV-2 invasion. The goal of this meta-analysis was to evaluate the safety profile of colchicine in COVID-19 patients using the gold-standard randomised-control trials.

Methods: Electronic databases (Pubmed, Google Scholar, and Cochrane) were systematically searched until June 2021 and RCTs were extracted. Outcomes of interest included all-cause mortality, COVID-19 severity, mechanical ventilation, C-reactive protein and D-dimer levels. Using a random-effects model, dichotomous outcomes were pooled using odds ratios (OR) through the generic …

Overcrowded Housing Increases Risk For Covid-19 Mortality: An Ecological Study., Karan Varshney, Talia Glodjo, Jenna Adalbert

College of Population Health Faculty Papers

OBJECTIVES: Overcrowded housing is a sociodemographic variable associated with increased infection and mortality rates from communicable diseases. It is not well understood if this association exists for COVID-19. Our objective was hence to determine the association between household overcrowding and risk of mortality from COVID-19, and this was done by performing bivariable and multivariable analyses using COVID-19 data from cities in Los Angeles County.

RESULTS: Bivariate regression revealed that overcrowded households were positively associated with COVID-19 deaths (standardized β = 0.863, p < 0.001). COVID-19 case totals, people aged 60+, and the number of overcrowded households met conditions for inclusion in the backwards stepwise linear regression model. Analysis revealed all independent variables were positively associated with mortality rates, primarily for individuals 60 + (standardized β

Csf-1 Maintains Pathogenic But Not Homeostatic Myeloid Cells In The Central Nervous System During Autoimmune Neuroinflammation, Daniel Hwang, Maryam S Seyedsadr, Larissa Ishikawa, Alexandra Boehm, Ziver Sahin, Giacomo Casella, Soohwa Jang, Michael V Gonzalez, James P Garifallou, Hakon Hakonarson, Weifeng Zhang, Dan Xiao, A M Rostami, Guang-Xian Zhang, Bogoljub Ciric

Department of Neurology Faculty Papers

SignificanceMultiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by accumulation of myeloid cells in the central nervous system (CNS). Both harmful and beneficial myeloid cells are present in EAE/MS, and a goal of MS therapy is to preferentially remove harmful myeloid cells. The receptor for CSF-1 (CSF-1R) is found on myeloid cells and is important for their survival. CSF-1R can bind two ligands, CSF-1 and IL-34, but it is not known whether their functions in EAE/MS differ. We found that blocking CSF-1 depleted only harmful myeloid cells in the CNS and suppressed EAE, …

Meloxicam Versus Celecoxib For Postoperative Analgesia After Total Knee Arthroplasty: Safety, Efficacy And Cost, Amer Haffar, Yale A Fillingham, Leigham Breckenridge, D'Andrew Gursay, Jess H Lonner

Rothman Institute Papers

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as part of multimodal analgesia in total knee arthroplasty (TKA). Selective cyclooxygenase (COX)-2 inhibitors (e.g., celecoxib) are believed to have fewer gastrointestinal (GI) adverse effects than nonselective NSAIDS. Meloxicam is less selective for COX-2 than celecoxib is and partially inhibits COX-1 at higher doses. Nonetheless, some surgeons prefer using nonselective NSAIDs because of their lower expense.

METHODS: Four thousand nine hundred ninety-four patients who underwent TKA between January 2015 and February 2020 and took either celecoxib (n = 3,174), meloxicam 15 mg/d (n = 1,819), or meloxicam 7.5 mg/d (n = 451) …

Genetic Evaluation For Hereditary Cancer Syndromes Among African Americans: A Critical Review, Ambreen Khan, Charles R Rogers, Carson D Kennedy, Ana Maria Lopez, Joanne Jeter

Department of Medical Oncology Faculty Papers

While hereditary cancer syndromes have been described and studied for centuries, the completion of the human genome project fueled accelerated progress in precision medicine due to the introduction of genetic testing in the 1990s, creating avenues for tailored treatments and medical management options. However, genetic testing has not benefited everyone equitably, with nearly all of the published work based on individuals of non-Hispanic White/European ancestry. There remains a gap in knowledge regarding the prevalence, penetrance, and manifestations of common hereditary cancer syndromes in the African-American population due to significant disparities in access and uptake of genetic testing. This review summarizes …

Overcrowded Housing Increases Risk For Covid-19 Mortality: An Ecological Study, Karan Varshney, Talia Glodjo, Jenna R Adalbert

College of Population Health Faculty Papers

Objectives: Overcrowded housing is a sociodemographic variable associated with increased infection and mortality rates from communicable diseases. It is not well understood if this association exists for COVID-19. Our objective was hence to determine the association between household overcrowding and risk of mortality from COVID-19, and this was done by performing bivariable and multivariable analyses using COVID-19 data from cities in Los Angeles County.

Results: Bivariate regression revealed that overcrowded households were positively associated with COVID-19 deaths (standardized β = 0.863, p < 0.001). COVID-19 case totals, people aged 60+, and the number of overcrowded households met conditions for inclusion in the backwards stepwise linear regression model. Analysis revealed all independent variables were positively associated with mortality rates, primarily for individuals 60 + (standardized β1 = 0.375, p = 0.001), followed by overcrowded households (standardized β2 = 0.346, p = 0.014), and total COVID-19 cases (standardized β3 = 0.311, p < 0.001). Our findings highlight that residing in overcrowded households may be an important risk factor for COVID-19 mortality. Public health entities should consider this population when allocating resources for prevention and control of COVID-19 mortality and future disease outbreaks.

A Mouse Model With Widespread Expression Of The C9orf72-Linked Glycine-Arginine Dipeptide Displays Non-Lethal Als/Ftd-Like Phenotypes, Brandie Morris Verdone, Maria Elena Cicardi, Xinmei Wen, Sindhu Sriramoji, Katelyn Russell, Shashirekha S Markandaiah, Brigid K Jensen, Karthik Krishnamurthy, Aaron R. Haeusler, Piera Pasinelli, Davide Trotti

Department of Neuroscience Faculty Papers

Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these …

Making Waves: How Ultrasound-Targeted Drug Delivery Is Changing Pharmaceutical Approaches., Lauren J Delaney, Selin Isguven, John R Eisenbrey, Noreen J Hickok, Flemming Forsberg

Department of Radiology Faculty Papers

Administration of drugs through oral and intravenous routes is a mainstay of modern medicine, but this approach suffers from limitations associated with off-target side effects and narrow therapeutic windows. It is often apparent that a controlled delivery of drugs, either localized to a specific site or during a specific time, can increase efficacy and bypass problems with systemic toxicity and insufficient local availability. To overcome some of these issues, local delivery systems have been devised, but most are still restricted in terms of elution kinetics, duration, and temporal control. Ultrasound-targeted drug delivery offers a powerful approach to increase delivery, therapeutic …

Change In Diuretic Dose After Initiation Of A Sglt2 Inhibitor In Patients With Heart Failure With Reduced Ejection Fraction, R. Wildemann, Pharmd, D. G. Karalis, Md, Facc, Fnla, N. Mirachi, Pa-C, B. Thoma, Pharmd, Bcps, Bccp

College of Pharmacy Posters

Study Purpose: To identify change in loop diuretic dose when initiating a SGLT2i in patients with HFrEF who are on a stable dose of loop diuretic in the outpatient setting

Jefferson Digital Commons Quarterly Report: January-March 2022, Larissa Gordon, Mslis, Med, Ma

Jefferson Digital Commons Reports

In this Issue:

• Articles
• Thesis/Dissertations
• Grand Rounds and Lectures
• Capstone Presentations
• Journals and Newsletters
• Posters
• Miscellaneous
• What People are Saying About the Jefferson Digital Commons

Adolescent Hiv Pre Exposure Prophylaxis Prescribing Practices Among Family Medicine Physicians: Limited Immediate Uptake, Marshal Miller, E. Cooper, S. Elsesser, A. Cunningham

Department of Family & Community Medicine Posters

This study aims to:

• Examine the adolescent PrEP prescribing practices and knowledge of family medicine physicians.
• Begin to identify areas that might be key targets for interventions which may lead to increased adolescent PrEP prescribing uptake.

Baroreflex Sensitivity In Facioscapulohumeral Muscular Dystrophy, Miguel Anselmo, Shandon Coffman, Mia Larson, Kathryn Vera, Emma Lee, Mary Mcconville, Michael Kyba, Manda L Keller-Ross

Department of Medicine Faculty Papers

Facioscapulohumeral muscular dystrophy (FSHD), a common form of muscular dystrophy, is caused by a genetic mutation that alters DUX4 gene expression. This mutation contributes to significant skeletal muscle loss. Although it is suggested that cardiac muscle may be spared, people with FSHD have demonstrated autonomic dysregulation. It is unknown if baroreflex function, an important regulator of blood pressure (BP), is impaired in people with FSHD. We examined if baroreflex sensitivity (BRS) is blunted in patients with FSHD. Thirty minutes of resting BP, heart rate, and cardiovagal BRS were measured in 13 patients with FSHD (age: 50 ± 13 years, avg …

Ten-Year Safety Of Pluripotent Stem Cell Transplantation In Acute Thoracic Spinal Cord Injury., Stephen L Mckenna, Reza Ehsanian, Charles Y Liu, Gary K Steinberg, Linda Jones, Jane S Lebkowski, Edward Wirth, Richard G Fessler

Department of Medicine Faculty Papers

OBJECTIVE: The purpose of this study was to evaluate the safety of oligodendrocyte progenitor cells (LCTOPC1) derived from human pluripotent stem cells administered between 7 and 14 days postinjury to patients with T3 to T11 neurologically complete spinal cord injury (SCI). The rationale for this first-in-human trial was based on evidence that administration of LCTOPC1 supports survival and potential repair of key cellular components and architecture at the SCI site.

METHODS: This study was a multisite, open-label, single-arm interventional clinical trial. Participants (n = 5) received a single intraparenchymal injection of 2 × 106 LCTOPC1 caudal to the epicenter of …

Occupational Therapy's Role In Serious Mental Illness, Sam Sutton, Anabelle Scalora, Tina Deangelis

Doctorate of Occupational Therapy Program Capstone Presentations

The intent of this electronic manual is to provide a client-centered and evidence-based resource to inform students, clinicians, and educators of occupational therapy’s unique role in working with adults with serious mental illness (SMI) and those experiencing psychosis. This manual, while not exhaustive, is designed to serve as a user-friendly resource for providing valid, equitable care to those with serious mental illness.

Objectives:

1. Provide an electronic resource that outlines the occupational therapy process when working with individuals with serious mental illness and supports inclusion and reimbursement for occupational therapy practitioners in this setting.
2. Define the multiple roles occupational therapy practitioners …

A Word From The Writing Team (April 2022), Pam Walter, Mfa, Liz Declan, Ma, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

• Upcoming Workshop
• News from the OPWPC
• Quick Reminder

National Trends In Pectus Excavatum Repair: Patient Age, Facility Volume, And Outcomes, Shale J. Mack, Brian M. Till, Charles Huang, Darshak Thosani, Uzma Rahman, Tyler Grenda, Nathaniel R. Evans Iii, Olugbenga Okusanya

Department of Surgery Faculty Papers

Background: There is limited data on the adult repair of pectus excavatum (PE). Existing literature is largely limited to single institution experiences and suggests that adults undergoing modified Nuss repair may have worse outcomes than pediatric and adolescent patients. Using a representative national database, this analysis is the first to describe trends in demographics, outcomes, charges, and facility volume for adults undergoing modified Nuss procedure.

Methods: Because of a coding change associated with ICD-10, a retrospective cohort analysis using the National Inpatient Sample (NIS) for patients 12 or older undergoing modified Nuss repair between 2016-2018 was possible. Pearson's χ2 and …

Improved Cotard Delusion And Motor Function In Parkinson’S Disease Following Electroconvulsive Therapy (Ect), Sunihidi Ramesh, Jeffrey Ratliff

Department of Neurology Faculty Papers

No abstract provided.

Immunomodulatory Effects And Clinical Benefits Of Intravenous Immunoglobulin In Myasthenia Gravis., Marinos C Dalakas, Andreas Meisel

Department of Neurology Faculty Papers

Introduction Myasthenia gravis (MG) is an antibody-mediated disease that develops in the majority of patients mainly as a result of acetylcholine receptor (AChR) autoantibodies. This process is mediated by a series of immunoregulatory events. Therapeutic targets for MG include suppression of circulating antibodies or antibody production, suppression of complement activation, and immunomodulation of cytokines or T cells. Intravenous immunoglobulin (IVIg) has an effect on all of these mechanisms. Areas covered This narrative review explores the broad immunomodulatory effects of IVIg in MG and provides an update on IVIg treatment for MG. Expert opinion IVIg has a range of immunomodulatory effects …

The Role Of The Complement System In Chronic Inflammatory Demyelinating Polyneuropathy: Implications For Complement-Targeted Therapies., Luis A Querol, Hans-Peter Hartung, Richard A Lewis, Pieter A Van Doorn, Timothy R Hammond, Nazem Atassi, Miguel Alonso-Alonso, Marinos Dalakas

Department of Neurology Faculty Papers

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common, heterogeneous, immune-mediated neuropathy, characterized by predominant demyelination of motor and sensory nerves. CIDP follows a relapsing-remitting or a progressive course and causes substantial disability. The pathogenesis of CIDP involves a complex interplay of multiple aberrant immune responses, creating a pro-inflammatory environment, subsequently inflicting damage on the myelin sheath. Though the exact triggers are unclear, diverse immune mechanisms encompassing cellular and humoral pathways are implicated. The complement system appears to play a role in promoting macrophage-mediated demyelination. Complement deposition in sural nerve biopsies, as well as signs of increased complement activation in …

Complement In Autoimmune Inflammatory Myopathies, The Role Of Myositis-Associated Antibodies, Covid-19 Associations, And Muscle Amyloid Deposits., Marinos Dalakas

Department of Neurology Faculty Papers

Introduction

The inflammatory myopathies (IM) have now evolved into distinct subsets requiring clarification about their immunopathogenesis to guide applications of targeted therapies

Areas Covered

Immunohistopathologic criteria of IM with a focus on complement, anti-complement therapeutics, and other biologic immunotherapies. The COVID19-triggered muscle autoimmunity along with the correct interpretation of muscle amyloid deposits is discussed.

Expert Opinion

The IM, unjustifiably referred as idiopathic, comprise Dermatomyositis (DM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). In DM, complement activation with MAC-mediated endomysial microvascular destruction and perifascicular atrophy is the fundamental process, while innate immunity activation factors, INF1 and …

Outcomes Of Ahmed Glaucoma Valve And Transscleral Cyclophotocoagulation In Neovascular Glaucoma, Wesam S Shalaby, Allen Y Ganjei, Brian Wogu, Jonathan S Myers, Marlene R Moster, Reza Razeghinejad, Daniel Lee, Natasha N Kolomeyer, Tarek E Eid, L Jay Katz, Aakriti Garg Shukla

Wills Eye Hospital Papers

Purpose: To determine the outcomes of Ahmed glaucoma valve (AGV) and transscleral diode cyclophotocoagulation (CPC) in neovascular glaucoma (NVG).

Methods: This was a single-center retrospective comparative case series involving chart review of consecutive patients who underwent AGV or CPC for treatment of NVG and had ≥6 months of follow-up. Surgical failure at 6 months, defined as an IOP of >21 or <6 mm Hg with hypotony maculopathy after 1 month, progression to no light perception (NLP) vision, glaucoma reoperation, or removal of AGV were the main outcome measures.

Results: In total, 121 eyes of 121 patients were included (70 AGV and 51 CPC). Baseline demographics, visual acuity (VA), and intraocular pressure (IOP) were comparable between groups. At 6 months, failure was significantly higher in the CPC group …